Dataset Information

Stable Isotope Probing Deuterium LC-MS/MS

ABSTRACT: Competition between commensal and pathogenic microbes for monosaccharides derived from mucus layer O-glycans as nutrient sources has been proposed as a mechanism by which the gut microbiota counteracts pathogen colonization. However, our understanding of the microbial interactions that determine competition for these sugars in complex microbial communities, and how to exploit such information to develop therapies, is limited. Here, we employed heavy water (D2O)-based activity labeling followed by automated Raman-Activated Cell Sorting of active (D-labeled) cells and metagenomics to identify mouse gut commensals that forage on O-glycan monosaccharides. Sequencing of cell-sorted fractions revealed members of the underexplored family Muribaculaceae as major mucin monosaccharide foragers, followed by members of Lachnospiraceae, Rikenellaceae and Bacteroidaceae families. We further show that the ability of these organisms to forage on mucosal sugars is well-supported by the presence of partial or complete catabolism pathways for O-glycan utilization in their genomes. Remarkably, administration of a 5-member bacterial consortium based on identified sialic acid and N-acetylglucosamine utilizers results in limited access of the gut pathogen Clostridioides difficile to mucosal sugars and in impaired pathogen colonization of antibiotic-treated mice. Our findings underscore the value of using targeted approaches to identify organisms performing key functions in the gut and to rationally design effective probiotic mixtures.

INSTRUMENT(S):

ORGANISM(S): Escherichia Coli

SUBMITTER: Nico Jehmlich

LAB HEAD: Nico Jehmlich

PROVIDER: PXD015215 | Pride | 2020-09-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	180714_NJ_Berry_Fuc_1.raw	Raw
	180714_NJ_Berry_Fuc_1.tabular	Other
	180714_NJ_Berry_Fuc_1_MAGS.tabular	Other
	180714_NJ_Berry_Fuc_1_mouse_mouse_gut.msf	Msf
	180714_NJ_Berry_Fuc_2.raw	Raw

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Publications

Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization.

Pereira Fátima C FC Wasmund Kenneth K Cobankovic Iva I Jehmlich Nico N Herbold Craig W CW Lee Kang Soo KS Lee Kang Soo KS Sziranyi Barbara B Vesely Cornelia C Decker Thomas T Stocker Roman R Warth Benedikt B von Bergen Martin M Wagner Michael M Berry David D

Nature communications 20201009 1

Many intestinal pathogens, including Clostridioides difficile, use mucus-derived sugars as crucial nutrients in the gut. Commensals that compete with pathogens for such nutrients are therefore ecological gatekeepers in healthy guts, and are attractive candidates for therapeutic interventions. Nevertheless, there is a poor understanding of which commensals use mucin-derived sugars in situ as well as their potential to impede pathogen colonization. Here, we identify mouse gut commensals that utili ...[more]

PMID: 33037214

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